Feasibility of intervention
Recruitment, retention, and completion rates
Between October 2020 and January 2021, 23 participants enrolled in the study and 20 participants completed the study. Three participants (13.04%) discontinued their participation: one withdrew from the study before commencing the intervention due to inability to commit for 6-week, and two participants were lost to follow-up before commencing the study. All 20 participants who completed the 6-week intervention completed all outcome measures (100%). The flow of study participants is outlined in Fig. 1.
Table 2 contains the descriptive characteristics of participants, stratified by those who completed (n = 20) and those who discontinued/withdrew (n = 3). Of the 20 participants who completed the study, 6 (30%) were male and 14 (70%) were female. The duration of MS varied from one to 45 years with the onset of LUTSs varied from one to 25 years. The most common type of MS was relapsing remitting (RRMS) (n = 12, 60%). All participants reported their urinary symptoms as a combination of symptoms (n = 20, 100%) whereas storage symptoms were reported in seven cases (35%). The most frequently reported symptom was urgency (n = 16, 80%) followed by frequency (n = 13, 65%) and nocturia (n = 12, 60%).
Table 2
Participant’s Demographic Characteristics (n=23)
Category
|
Variable
|
Participants completed the study (20):
n (%)
|
Participants lost to follow (3):
n (%)
|
Gender
|
Female
|
14 (70%)
|
2 (66.67%)
|
Male
|
6 (30%)
|
1 (33.33%)
|
Age
|
18–24
|
-
|
-
|
25–34
|
-
|
-
|
35–44
|
6 (30%)
|
2 (66.67%)
|
45–54
|
6 (30%)
|
1 (33.33%)
|
55–64
|
6 (30%)
|
-
|
65–74
|
1 (5%)
|
-
|
75–84
|
-
|
-
|
85 or Older
|
1 (5%)
|
-
|
Marital Status
|
Single
|
2 (10%)
|
2 (66.67%)
|
Married
|
17 (85%)
|
1 (33.33%)
|
Widowed
|
-
|
-
|
Divorced
|
1 (5%)
|
-
|
Separated
|
-
|
-
|
MS type
|
RR MS
|
12 (60%)
|
2 (66.67%)
|
PP MS
|
5 (25%)
|
1 (33.33%)
|
SP MS
|
3 (15%)
|
-
|
PR MS
|
-
|
-
|
MS diagnosis in years
|
1–5
|
2 (10%)
|
-
|
6–10
|
8 (40%)
|
1 (33.33%)
|
11–15
|
3 (15%)
|
2 (66.67%)
|
16–20
|
3 (15%)
|
-
|
21–25
|
2 (10%)
|
-
|
26–30
|
1 (5%)
|
-
|
31–35
|
-
|
-
|
36–40
|
-
|
-
|
41–45
|
1 (5%)
|
-
|
LUTSs main
|
Urgency
|
16 (80%)
|
3 (100%)
|
Frequency
|
13 (65%)
|
2 (66.67%)
|
Nocturia
|
12(60%)
|
1 (33.33%)
|
Urge incontinence
|
6 (30%)
|
1 (33.33%)
|
Terminal dribbles
|
4 (20%)
|
-
|
Hesitancy
|
5 (25%)
|
-
|
Feeling of incomplete bladder emptying
|
8 (40%)
|
1 (33.33%)
|
Urinary incontinence
|
5 (25%)
|
2 (66.67%)
|
Double void
|
4 (20%)
|
1 (33.33%)
|
LUTSs in years
|
1–5
|
6 (30%)
|
1 (33.33%)
|
6–10
|
9 (45%)
|
-
|
11–15
|
3 (15%)
|
2 (66.67%)
|
16–20
|
1 (5%)
|
-
|
21–25
|
1 (5%)
|
-
|
Previous TX
|
None
|
4 (20%)
|
1 (33.33%)
|
Pharmacologic
|
7 (35%)
|
1 (33.33%)
|
Non-Pharmacologic:
|
3 (15%)
|
1 (33.33%)
|
Exercises
|
|
Nerve stimulation with another treatment (Exercise and/or Catheterization)
|
3 (15%)
|
-
|
Behavioural
|
3 (15%)
|
-
|
Current TX
|
None
|
6 (30%)
|
2 (66.67%)
|
Pharmacologic
|
9 (45%)
|
1 (33.33%)
|
Pharmacologic with Catheterization
|
2 (10%)
|
-
|
Non-Pharmacologic:
Exercises
|
2 (10%)
|
-
|
Nerve stimulation
|
-
|
-
|
Behavioural
|
1 (5%)
|
-
|
Prophylactic
|
Yes
|
3 (15%)
|
-
|
No
|
17 (85%)
|
3 (100%)
|
Comorbidities
|
None
|
8 (40%)
|
1 (33.33 %)
|
Thyroid related issues
|
2 (10%)
|
1 (33.33%)
|
Hypertension
|
1 (5%)
|
1 (33.33%)
|
Reynolds syndrome
|
1 (5%)
|
|
Cancer
|
1 (5%)
|
-
|
Foot drop/mobility
|
2 (10%)
|
-
|
Migraine
|
1 (5%)
|
1 (33.33%)
|
hearing impairment
|
1 (5%)
|
-
|
Bowel related issues/ duodenal ulcer
|
3 (15%)
|
-
|
PDDS-Mobility
|
(0) Normal
|
3 (15%)
|
-
|
(1) Mild disability
|
1 (5%)
|
|
(2) Moderate disability
|
3 (15%)
|
1(33.33%)
|
(3) Gait disability
|
2 (10%)
|
|
(4) Early cane
|
3 (15%)
|
|
(5) Late cane
|
4 (20%)
|
1 (33.33%)
|
(6) Bilateral support
|
3 (15%)
|
|
(7) Wheelchair
|
1 (5%)
|
1 (33.33%)
|
(8) Bedridden
|
-
|
|
MS, multiple sclerosis; RR, relapsing–remitting; SP, secondary progressive; PP, primary progressive; PR, progressive relapsing; LUTSs, lower urinary tract symptoms; PDDS, Patient Determined Disease Step
Adverse events
There were no reported stimulation-related adverse events in the participants during the study intervention phase. Two (10%) participants reported skin reactions in the site of the stimulation with (n = 1) redness after first stimulation session and (n = 1) dry skin at the stimulation site that cleared up after 8 days. This did not impact treatment adherence.
Adherence to the treatment protocol
The adherence to the 18 sessions amongst 20 participants was 100%.
Acceptability of TTNS application
The responses to the participant satisfaction questionnaire (Likert scale) are shown in Table 3. The median score was 5 points (IQR = 0.25 points) regarding the ease of use of the device, indicating that participants strongly agreed that the device was easy to use. Median scores of 5 points were also recorded for acceptability of the frequency, duration, and timing of the intervention. Overall, participants were very satisfied with the intervention (median score = 5 points, IQR = 0 points).
Table 3
Acceptability (satisfaction) survey (n = 20)
Questions
|
Median score (IQR)
|
Q1. Please, tick the appropriate box that indicate your satisfaction with nerve stimulation - The device is easy to use.
|
5(0.25)
|
Q2. Please, tick the appropriate box that indicate your satisfaction with nerve stimulation - The device is comfortable to use.
|
4.5(1)
|
Q3. Please, tick the appropriate box that indicate your satisfaction with nerve stimulation - Application of tibial nerve stimulation at home was acceptable.
|
5(1)
|
Q4. Please, tick the appropriate box that indicate your satisfaction with nerve stimulation - Using the tibial nerve stimulation for 30 mins 3 times/ week is acceptable.
|
5(0.25)
|
Q5. Please, tick the appropriate box that indicate your satisfaction with nerve stimulation - Using the tibial nerve stimulation for 6 weeks is acceptable.
|
5(1)
|
Q6. Please, tick the appropriate box that indicate your satisfaction with nerve stimulation - Overall, I am satisfied with the device.
|
5(0)
|
5-point Likert scale employed across questions (score of 1= “strongly disagree”; 2= “disagree”; 3= “neutral”; 4= “agree”; 5= “strongly agree |
Secondary outcome measures
Changes in bladder storage symptoms reported using 3-day bladder diary and PPIUS.
Table 4 displays the baseline and post-intervention score across all outcome measures. Daily average urination, urinary frequency in 24hrs, changed from a daily median of 10 times (SD = 3) to 8 times (SD = 3). Median daily urinary urgency changed from 6 times (IQR = 5.8) at baseline to 2 times daily (IQR = 4) post-intervention. No changes were observed in the daily mean episodes of nocturia (mean = 1 episode, SD = 1).
Table 4
Scores of the outcome measures (n = 20)
3- day bladder diary scores
|
|
Baseline
|
Post-intervention (week 6)
|
Daily average urinary frequency (24hrs): mean (SD)
|
10 (3)
|
8 (3)
|
Daily average urgency: median (IQR)
|
6 (5.8)
|
2 (4)
|
Daily average urinary incontinence: median (IQR)
|
0 (1.3)
|
0 (0)
|
Daily average nocturia: mean (SD)
|
1 (1)
|
1 (1)
|
Daily average fluid intake: mean (SD)
|
1585 (604.5)
|
1504 (489)
|
Daily average fluid intake: Caffeinated drinks: mean (SD)
|
542 (367)
|
547 (360)
|
Daily average fluid intake: non-caffeinated drinks: mean (SD)
|
1043 (566)
|
957 (491)
|
Patient Perception of Intensity of Urgency Scale (PPIUS)
|
|
Baseline
|
Post-intervention (week 6)
|
Daily average total scores PPIUS: median (IQR)
|
2 (1)
|
2 (1)
|
Daily average severe urgency grade (3): median (IQR)
|
3 (4)
|
1 (1)
|
Daily average urge urinary incontinence grade (4): median (IQR)
|
0 (0.6)
|
0 (0)
|
Daily average severe urgency + urge urinary incontinence grade (3 + 4): median (IQR)
|
3 (3.4)
|
1 (1)
|
International Consultation on Incontinence Questionnaire Over active bladder (ICIQ-OAB) scores
|
|
Baseline
|
Post-intervention (week 6)
|
Total score ICIQ-OAB: Median (IQR)
|
8 (2.25)
|
4 (2.5)
|
Q1. Frequency: median (IQR)
|
1 (2)
|
1 (2)
|
Q2. Nocturia: median (IQR)
|
2 (2)
|
1 (0.5)
|
Q3. Urgency: median (IQR)
|
3 (1)
|
1 (1)
|
Q4. Urge urinary incontinence: median (IQR)
|
2 (1)
|
1 (1)
|
Kings Health Questionnaire (KHQ)
|
|
Baseline
|
Post-intervention (week 6)
|
Total Score: Part-one: Mean (SD); Median (IQR)
|
5.8 (1.2); 6 (1.25)
|
5(1.27) *; 5 (2) *
|
Total Score: Part-two: Mean (SD); Median (IQR)
|
44.6 (8.9); 43 (10)
|
28.4 (8.5); 27.5 (8)
|
Total Score: Part-three: Mean (SD); Median (IQR)
|
10 (2.7) *; 10 (4.25) *
|
7.55 (4) *; 6.5(5.25) *
|
SD : standard deviation; IQR: interquartile range. |
*: indicates that data are not normally distributed |
The daily median urgency scores (grade 3) assessed by PPIUS changed from 3 points (IQR = 4) to 1 point (IQR = 1) post-intervention with no changes were reported in daily median urgency urinary incontinence (UUI). Daily average fluid consumption remained stable across both timepoints.
Changes in bladder storage symptoms reported using ICIQ-OAB.
The ICIQ-OAB median scores are summarised in Table 4. The overall median (IQR) scores for urinary symptoms as measured by the ICIQ-OAB changed from 8 points (IQR = 2.25) at baseline to 4 points (IQR = 2.5) post-intervention.
Changes in health-related quality of life scores for urinary symptoms reported by KHQ.
The KHQ scores at baseline and post-intervention are summarized in Table 4. No changes in mean/median total scores were reported in the KHQ-Part- one. The median and mean scores of part-two changed from 43 points (IQR = 10) and 44.6 points (SD = 8.9) at baseline to 27.5 points (IQR = 8) and 28.4 points (SD = 8.5) at the end of week 6, respectively. Part- three showed changes from 10 points (IQR = 4.25) and 10 points (SD = 2.7) at baseline to 6.5 points (IQR = 5.25) and 7.55 (SD = 4) post-intervention, respectively.